title: Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents.
abstract: BACKGROUND
  Reported overall survival (OS) rates of patients with localized Ewing sarcoma family of tumors (ESFT) are >80% when treated with the MSKCC P6 protocol. However, it has been associated with a 5.8% incidence of secondary leukemias. A modified P6 (mP6) protocol with reduced exposure to chemotherapy is presented.
  
  
  METHODS
  Thirty-one newly diagnosed ESFT patients were enrolled onto this phase II, single-arm, non-randomized protocol. Courses 1, 2 and 4 consisted of cyclophosphamide 4.2 g/m², doxorubicin 75 mg/m², and vincristine 2 mg/m² (CDV). Cycles 3 and 5 consisted of ifosfamide 9 g/m² and etoposide 500 mg/m² (IE). Course 5 ifosfamide was 14 g/m² if necrosis was <90%.
  
  
  RESULTS
  Twenty-four patients had loco-regional disease and seven had metastases. The 4-year event-free survival (EFS) rate for patients with localized tumors is 83% and overall survival (OS) is 92%. The 3-year EFS rate for patients with distant metastases is 28% and OS rate is 42%. EWS-FLI1 fusion genes were detected in 17 cases (74%) and EWS-ERG in six cases (26%). Type 1 EWS-FLI1 variant was present in 6/7 metastatic patients and 3/16 loco-regional cases (P = 0.001). None of the patients experienced tumor progression before remission. All relapses occurred within 2 years from the end of treatment and local relapses (n = 3) happened in patients who did not receive radiation therapy. No secondary malignancies have been observed, median follow-up of 4.3 years for surviving patients.
  
  
  CONCLUSIONS
  In this pilot study, the mP6 protocol produced a complete remission rate of 83% at 4 years in non-metastatic ESFT reducing the risk of secondary malignancies.
authors.affiliation: Department of Oncology, Hospital Sant Joan de Déu, Barcelona, Spain. jmora@hsjdbcn.org
authors.forename: Jaume
authors.initials: J
authors.lastname: Mora
authors.forename: Carmen
authors.initials: C
authors.lastname: de Torres
authors.forename: Andreu
authors.initials: A
authors.lastname: Parareda
authors.forename: Ferran
authors.initials: F
authors.lastname: Torner
authors.forename: Patricia
authors.initials: P
authors.lastname: Galván
authors.forename: Eva
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Teresa
authors.initials: T
authors.lastname: Cardesa
authors.forename: Héctor
authors.initials: H
authors.lastname: Salvador
authors.forename: Mariona
authors.initials: M
authors.lastname: Suñol
authors.forename: Ramon
authors.initials: R
authors.lastname: Huguet
authors.forename: Ofelia
authors.initials: O
authors.lastname: Cruz
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007223:Infant; D008297:Male; D009362:Neoplasm Metastasis; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000378:metabolism; D034802:RNA-Binding Protein EWS / Q000378:metabolism; D012008:Recurrence; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide